中华医学遗传学杂志
中華醫學遺傳學雜誌
중화의학유전학잡지
CHINESE JOURNAL OF MEDICAL GENETICS
2012年
5期
519-523
,共5页
马云霞%周永安%张景萍%张全斌%刘薇拉%任彩芬%李小雨
馬雲霞%週永安%張景萍%張全斌%劉薇拉%任綵芬%李小雨
마운하%주영안%장경평%장전빈%류미랍%임채분%리소우
Leber遗传性视神经病变%线粒体DNA%原发性突变位点%测序分析
Leber遺傳性視神經病變%線粒體DNA%原髮性突變位點%測序分析
Leber유전성시신경병변%선립체DNA%원발성돌변위점%측서분석
Leber's hereditary optic neuropathy%Mitochondrial DNA%Common mutations%DNA sequencing
目的 通过对Leber遗传性视神经病变(Leber's hereditary optic neuropathy,LHON)线粒体DNA ND4 11778G＞A、ND1 3460G＞A和ND6 14484T＞C 3个原发性突变位点序列分析,阐明LHON患者发病的分子机理.方法 PCR扩增35例患者的上述3个原发性突变位点所在的区段,PCR产物直接测序分析.结果 35例患者中,6例存在ND4 11778 G＞A突变位点,1例存在ND1 3460 G＞A突变位点,未检出ND6 14484 T＞C突变位点,3个原发性突变位点的检出率为20.0％(7/35).35例患者均存在ND4 11719G＞A同义突变,除此突变位点外,23例(65.7％)患者共计筛出21个突变位点,2种突变类型.其中13例患者存在单个突变位点,8例存在2个突变位点,2例存在3个突变位点.21个突变位点中,ND4 11778G＞A突变频率最高,为28.6％(6/21); ND1 3552 T＞A、ND6 14470 T＞C、ND4 11794 T＞C、ND1 3497 C＞T和3644 T＞C位点突变频率依次为19.0％(4/21)、19.0％(4/21)、14.3％(3/21)、9.5％(2/21)和9.5％(2/21).3例存在ND4 11794 T＞C突变位点的患者,2例为异质性突变,1例为同质性突变.结论 LHON患者线粒体DNA ND4 11778G＞A、ND1 3460G＞A和ND6 14484T＞C 3个原发性致病突变中,以ND4 11778 G＞A为主；继发性突变位点ND1 3552 T＞A或ND1 3644 T＞C单独或协同原发性突变位点ND4 11778 G＞A导致LHON的发生,与单纯携带ND4 11778 G＞A的患者相比视力受损较弱.
目的 通過對Leber遺傳性視神經病變(Leber's hereditary optic neuropathy,LHON)線粒體DNA ND4 11778G＞A、ND1 3460G＞A和ND6 14484T＞C 3箇原髮性突變位點序列分析,闡明LHON患者髮病的分子機理.方法 PCR擴增35例患者的上述3箇原髮性突變位點所在的區段,PCR產物直接測序分析.結果 35例患者中,6例存在ND4 11778 G＞A突變位點,1例存在ND1 3460 G＞A突變位點,未檢齣ND6 14484 T＞C突變位點,3箇原髮性突變位點的檢齣率為20.0％(7/35).35例患者均存在ND4 11719G＞A同義突變,除此突變位點外,23例(65.7％)患者共計篩齣21箇突變位點,2種突變類型.其中13例患者存在單箇突變位點,8例存在2箇突變位點,2例存在3箇突變位點.21箇突變位點中,ND4 11778G＞A突變頻率最高,為28.6％(6/21); ND1 3552 T＞A、ND6 14470 T＞C、ND4 11794 T＞C、ND1 3497 C＞T和3644 T＞C位點突變頻率依次為19.0％(4/21)、19.0％(4/21)、14.3％(3/21)、9.5％(2/21)和9.5％(2/21).3例存在ND4 11794 T＞C突變位點的患者,2例為異質性突變,1例為同質性突變.結論 LHON患者線粒體DNA ND4 11778G＞A、ND1 3460G＞A和ND6 14484T＞C 3箇原髮性緻病突變中,以ND4 11778 G＞A為主；繼髮性突變位點ND1 3552 T＞A或ND1 3644 T＞C單獨或協同原髮性突變位點ND4 11778 G＞A導緻LHON的髮生,與單純攜帶ND4 11778 G＞A的患者相比視力受損較弱.
목적 통과대Leber유전성시신경병변(Leber's hereditary optic neuropathy,LHON)선립체DNA ND4 11778G＞A、ND1 3460G＞A화ND6 14484T＞C 3개원발성돌변위점서렬분석,천명LHON환자발병적분자궤리.방법 PCR확증35례환자적상술3개원발성돌변위점소재적구단,PCR산물직접측서분석.결과 35례환자중,6례존재ND4 11778 G＞A돌변위점,1례존재ND1 3460 G＞A돌변위점,미검출ND6 14484 T＞C돌변위점,3개원발성돌변위점적검출솔위20.0％(7/35).35례환자균존재ND4 11719G＞A동의돌변,제차돌변위점외,23례(65.7％)환자공계사출21개돌변위점,2충돌변류형.기중13례환자존재단개돌변위점,8례존재2개돌변위점,2례존재3개돌변위점.21개돌변위점중,ND4 11778G＞A돌변빈솔최고,위28.6％(6/21); ND1 3552 T＞A、ND6 14470 T＞C、ND4 11794 T＞C、ND1 3497 C＞T화3644 T＞C위점돌변빈솔의차위19.0％(4/21)、19.0％(4/21)、14.3％(3/21)、9.5％(2/21)화9.5％(2/21).3례존재ND4 11794 T＞C돌변위점적환자,2례위이질성돌변,1례위동질성돌변.결론 LHON환자선립체DNA ND4 11778G＞A、ND1 3460G＞A화ND6 14484T＞C 3개원발성치병돌변중,이ND4 11778 G＞A위주；계발성돌변위점ND1 3552 T＞A혹ND1 3644 T＞C단독혹협동원발성돌변위점ND4 11778 G＞A도치LHON적발생,여단순휴대ND4 11778 G＞A적환자상비시력수손교약.
Objective To screen for genetic mutations in 35 patients with Leber's hereditary optic neuropathy (LHON).Methods Polymerase chain reaction and DNA sequencing were used to screen for the presence of mitochondrial DNA mutations.Results The total detection rate of top 3 common LHON mutations were 20.0％,which included 6 cases of ND4 11778 G＞A,1 case of ND1 3460 G＞A.NoND6 14484 T＞C mutation was detected.A ND4 G11719A synonymous mutation was found in all patients.In addition,21 other mutations were discovered among 23 patients,among which 13 had a single mutation,8 had a second mutations,and 2 had a third mutation.Among the 21 mutations,ND4 11778 G＞A had a frequency of 28.6％(6/21).ND1 3552 T＞A,ND6 14470 T＞C,ND4 11794 T＞C,ND1 3497 C＞T and 3644 T＞C respectively had a frequency of 19.0％(4/21).19.0％(4/21),14.3％(3/21),9.5％(2/21) and 9.5％(2/21).Among the 3 patients who harbored a ND4 11794 T＞C mutation,2 were heteroplasmic and one was homoplasmic in nature.Conclusion The ND4 11778 G＞A mutation is common in the Top "3"primary mutations of patients with LHON.Candidate LHON mutation ND1 3552 T＞ A or ND1 3644 T＞C resulted in LHON pathogenesis as single or synergistic effect.The visual impairment at onset of the disease with candidate mutation were better than the eyes with the ND4 11778 G＞A mutation.
